Multipotential neural stem cells (NSCs), capable of differentiating into all neural cell types, are present throughout the development of the central nervous system (CNS) and are maintained in limited populations into adulthood, To date, the identity of these cells remains unclear due to the lack of a universally expressed NSC marker that is found in all CNS progenitors regardless of their regional localization, Our lab, and others, have shown that SOX2, an HMG box transcription factor, is expressed in all NSCs at all stages of development and is necessary to maintain their progenitor identity. Our hypothesis is that, using SOX2 as a universal stem cell marker, we are capable of isolating and characterizing NSCs in vivo. The aims of this proposal are to test our hypothesis by generating a mouse line that utilizes a genetic method of ablating NSC populations in vivo. The Sox2-DTA mouse will conditionally express the cellular toxin gene encoding the Diphtheria Toxin A subunit (DTA) under the control of Sox2 regulatory regions only in cells expressing Cre- recombinase. By breeding our line with different cre-expressing lines, we will be able to selectively ablate populations of cells thought to contain NSCs and analyze their loss or function in vivo. [unreadable] [unreadable]